Abstract
The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology 1,2 . Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14 + CD16 + inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.
【초록키워드】 neutralizing antibody, Monocytes, SARS-CoV-2, mRNA vaccination, immune response, vaccination, innate immune response, Neutralizing antibodies, mRNA vaccine, B.1.351, T cells, transcriptomics, interferon, immune system, CD4, Emergency use authorization, immunization, mRNA vaccines, Antigen, monocyte, innate immune system, BNT162b2, T cell, immune responses, pathway, Cluster, innate antiviral immunity, plasma, Adaptive immune response, single-cell, CD8 T cells, Neutralizing antibody response, booster, booster vaccination, CD16, Frequency, Concentration, Analysis, Inflammatory, CD8 T cell, inflammatory monocytes, transcription factor, transcription factors, secondary immunization, B.1.351 variant, second dose, These data, protective immune response, neutralizing antibody responses, wild-type SARS-CoV-2, AP-1, CD14, myeloid cell, approach, landmark, Pfizer-BioNTech mRNA vaccine, transcriptional, robust, stimulated, greater, reduced, less, demonstrated, elicit, increase in, stimulate, evidenced, significant increases in, healthy volunteer, 【제목키워드】 Human, BNT162b2 mRNA vaccine, System,